Summary

This well-characterized model of Down's syndrome develops elevated APP but lacks appreciable β-amyloid pathology. The mice are aneuploid and carry the translocation chromosome, Mmu1716 (1716), as a freely segregating, supernumerary chromosome. The 1716 chromosome carries approximately 13.4 Mb of distal chromosome 16, from Mrpl39 to Zfp295, fused with about 10 Mb of chromosome 17, just proximal to the centromere. The precise locations of the chromosome 16 and chromosome 17 breakpoints are 84,351,351 bp and 9,426,822 bp, respectively (Reinholdt et al., 2011).

These mice are affected by reduced birthweight, muscular trembling, male sterility, and an abnormal facial appearance (Davisson et al., 1990). From a young age, many deficits in behavior and cognition have also been observed. They have spatial learning and memory deficits as assessed by the Morris water maze and the radial arm maze, show developmental delay in sensorimotor milestones, and exhibit locomotor hyperactivity, lack of behavioral inhibition, and stereotypic behavior.

The brains of Ts65Dn mice are grossly normal. Neuropathologically they show age-dependent cholinergic neurodegeneration in the basal forebrain between six and twelve months of age (Holtzman et al., 1996). They also have a reduction in nerve growth factor (NGF) in the basal forebrain at this time (Hunter et al., 2003). Alterations in synaptic plasticity and adult neurogenesis have also been reported. They do not have evidence of β-amyloid pathology (Holtzman et al., 1996) despite age-related elevation of APP and Aβ in the hippocampus (Hunter et al., 2003).

These mice are on a genetic background that leads to blindness in about 25 percent of progeny due to the retinal degeneration allele Pde6brd1. Mice that are homozygous for the rd1 allele are affected. An alternative strain is available (The Jackson Lab Stock# 005252) with a virtually identical genetic background except that it is wild-type for Pde6brd1. Only subtle phenotypic differences have been observed between the two strains (Costa et al., 2010).